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Betaine Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibiting Dendritic Cell–Derived IL-6 Production and Th17 Differentiation

Cuixia Yang, Weiming Lai, Jinfeng Zhou, Xinyuan Zheng, Yingying Cai, Wanjie Yang, Sirong Xie, Yuan Gao and Changsheng Du
J Immunol January 12, 2018, ji1700920; DOI: https://doi.org/10.4049/jimmunol.1700920
Cuixia Yang
Putuo District People’s Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
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Weiming Lai
Putuo District People’s Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
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Jinfeng Zhou
Putuo District People’s Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
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Xinyuan Zheng
Putuo District People’s Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
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Yingying Cai
Putuo District People’s Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
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Wanjie Yang
Putuo District People’s Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
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Sirong Xie
Putuo District People’s Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
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Yuan Gao
Putuo District People’s Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
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Changsheng Du
Putuo District People’s Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
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Abstract

IL-17–secreting T cells (Th17 cells) play a pathogenic role in multiple autoimmune diseases, including multiple sclerosis (MS), and dendritic cell (DC)-derived cytokines play pivotal roles in promoting the differentiation of naive CD4+ T cells into Th cell subsets (Th1 and Th17). Therefore, small molecules blocking the key cytokines produced by DCs will be beneficial in MS. In this article, we report that betaine treatment ameliorates MS pathogenesis by inhibiting DC-derived IL-6 production and Th17 differentiation. Using experimental autoimmune encephalomyelitis, a widely used mouse model of MS, we found that, compared with the vehicle-treated group, betaine-treated mice exhibited less severe experimental autoimmune encephalomyelitis symptoms, including lower clinical scores, reduced leukocyte infiltration, and less extensive demyelination in the CNS. Moreover, a significantly lower percentage of Th17 cells, one of the major pathogenic effector cells in MS progression, was observed in the peripheral immune system and in the CNS. Interestingly, in the in vitro Th17-differentiation assay, no significant change in Th17 cells was observed between the vehicle- and betaine-treated groups, whereas in the in vitro DC culture experiment, betaine treatment significantly decreased DC-derived IL-6 production. In the DC–T cell coculture experiment, a significantly decreased Th17 differentiation was observed upon betaine treatment. All of these data demonstrated that betaine inhibited Th17 differentiation indirectly by reducing IL-6 production by DCs. In brief, our findings demonstrated the pivotal roles of betaine in modulating MS pathogenesis and suggested that it may serve as a potential novel drug candidate for the treatment of MS.

  • Received June 27, 2017.
  • Accepted December 15, 2017.
  • Copyright © 2018 by The American Association of Immunologists, Inc.

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The Journal of Immunology: 200 (8)
The Journal of Immunology
Vol. 200, Issue 8
15 Apr 2018
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Betaine Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibiting Dendritic Cell–Derived IL-6 Production and Th17 Differentiation
Cuixia Yang, Weiming Lai, Jinfeng Zhou, Xinyuan Zheng, Yingying Cai, Wanjie Yang, Sirong Xie, Yuan Gao, Changsheng Du
The Journal of Immunology January 12, 2018, ji1700920; DOI: 10.4049/jimmunol.1700920

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Betaine Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibiting Dendritic Cell–Derived IL-6 Production and Th17 Differentiation
Cuixia Yang, Weiming Lai, Jinfeng Zhou, Xinyuan Zheng, Yingying Cai, Wanjie Yang, Sirong Xie, Yuan Gao, Changsheng Du
The Journal of Immunology January 12, 2018, ji1700920; DOI: 10.4049/jimmunol.1700920
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Print ISSN 0022-1767        Online ISSN 1550-6606